Cytokines and chemokines are proteins made by cells that affect the behavior of other cells. Cytokines made by leukocytes and lymphocytes are often called interleukins (IL) or lymphokines. Cytokines act on specific cytokine receptors on the cells they affect. Binding to the cognate receptor induces activity in the cell such as growth, differentiation, migration or death. Several cytokines and chemokinesplay key roles in mediating acute inflammatory reactions, namely IL-1 beta, TNF-alpha, IL-6, IL-11, IL-12, interferon gamma, IL-8 and other chemokines. Receptors for hemopoietic growth factors, GCSF, and GM-CSF share structural similarity with cytokine receptors and influence the production and function of leukocytes in inflammation.
The production of pro-inflammatory cytokines and chemokines by cells of the innate immune system play an important role in mediating the initial host defense against invading pathogens. Furthermore, the inability to regulate the nature or duration of the host's inflammatory response can often mediate detrimental host effects as observed in acute and chronic inflammatory diseases. For example, in the early stages of sepsis, the host's inflammatory response is believed to be in a hyperactive state with a predominant increase in the production of pro-inflammatory cytolcines that mediate host tissue injury and lethal shock. Thus, the ability of the innate immune system to dictate the levels of pro- and anti-inflammatory cytokine production is critical in limiting or modulating the nature of the host inflammatory response. This ability is conferred by a family of physiologic intracellular proteins termed suppressors of cytokine signaling (SOCSs).
There is a need in the art for methods and compositions capable of inhibiting cytokine-induced signaling, thereby controlling inflammation and associated disorders.